Preparation of biguanides



United States Patent PREPARATION OF BIGUANIDES 'Ingenuin Hechenbleikner,Adams, Mass, and Donald W.

Kaiser, Hamden, Comm, assignors to American Cyanamid Company, New York,N. Y., a corporation of Maine N0 Drawing. Application September 20,1955, Serial No. 535,509

Claims. (Cl. 260-565) The present invention relates to a method ofpreparing biguanidcs which are capable of representation by the genericformula wherein R1 stands for an alkyl radical having from 1 to 18carbon atoms, R2 stands for hydrogen or an alkyl radical having from 1to 18 carbon atoms, and R3 and R4 stand for hydrogen, an aryl radical oran alkyl radical havingfrom 1 to 18 carbon atoms.

In accordance with the present invention, the biguanide compounds may bereadily prepared by reacting in an inert solvent analkylguanylchloroformamidine hydrochloride of the formula in which R1and R have the meanings shown above, with a member of the groupconsisting of ammonia, a primary amine of the formula RsNHz and asecondary amine of the formula R3R4NH wherein R3 and R4 represent anaryl radical or an alkyl radical having from 1 to 18 carbon atoms. Ifnecessary or desirable, the hydrochloride salt of the biguanide thusobtained is easily converted to the free base by treatment with analkali metal hydroxide.

Methods of preparing the alkylguanylchloroformamidine hydrochloridesemployed in the present process are disclosed in copending application,Serial No. 358,549, filed May 29, 1953, now abandoned, byHechenbleikner, one of the present inventors.

For example, tetraethylguanylchloroforrnamidine hydrochloride is formedby reacting diethylcyanamide with hydrogen chloride at a temperaturewithin the range of from 60 to 150 C. The reaction may be illustrated asfollows:

1,3-dimethylguanylchloroformamidine hydrochloride1,3-dipropylguanylchloroformamidine hydrochloride 2,768,205 PatentedOct. 23, 1956 hydro- Amines typical of those capable of undergoing thereaction of the present invention are methylamine, dimethylamine,ethylamine, diethylamine, methylethylamine, methylisobutylamine,propylamine, dipropylamine, isopropylamine, ethylpropylarnine,butylamine, dibutylamine, amylamine, hexylamine, 2-ethylhexylamine,octylamine,

'dioctylamine, decylarnine, dodecylamine, octadecylamine,

didodecylamine, dioctadecylamine, aniline, o-chloroaniline,p-bromoaniline, p-nitroaniline, N-methylaniline, N-ethylaniline,diphenylamine, Nmethyl-a-naphthylamine, a-naphthylamine,,B-naphthylamine, di-B-naphthylamine, o-anisidine, p-phenetidine,N-methyl-p-pl1enetidine, the toluidines and xylidines.

In the present process .the optimum reaction temperature varies somewhatwith the specific reactants employed, but in most reactions atemperature within the range of from about 10 C. to about C. ispreferred. Compounds which may be employed as solvents in the'processare benzene, toluene, acetonitrile, tetrahydrofurane, dioxane, water andthe lower aliphatic monohydric alcohols such as the methyl, ethyl,propyl and butyl alcohols.

The invention is further illustrated, but not limited, by the followingexamples:

EXAMPLE 1 1 ,1 ,5,S-tetmmethylbiguanide A solution of 21.3 g. oftetramethylguanylchloroformamidine hydrochloride in 50 cc. of water wasadded slowly with stirring to .50 cc. of 28.6% aqueous ammonia. Thetemperature of the mixture rose rapidly to 65 C. The reaction mixturewas then allowed to stand in an evaporating vessel at room temperaturefor 72 hours. The solid residue wa leached with boiling isopropanol.Evaporation of the filtrate gave 17 g. (88% yield) of the1,1,5,5-tetramethylbiguanide hydrochloride which melted at 2122l5 C. Thefree base was formed by treating the hydrochloride salt with sodiumhydroxide in aqueous solution.

EXAMPLE 2 1,1,5,5-tetraethylbiguanide A solution of 13.4 g. oftetraethylguanylchloroformamidine hydrochloride in 50 cc. of methanolwas added to 25 cc. of 28.6% aqueous ammonia at 5 C. The temperature-ofthe mixture rose quickly to 40 C. After standing at room temperature forone hour, the reaction mixture was poured into 200 cc. of water, andthen made alkaline by the addition of sodium hydroxide. The precipitatedbiguanide was separated by filtration and recrystallized from hexane.The white crystalline product melted at 79-80" C.

EXAMPLE 3 1,5-di-t-butylbiguanide 26.9 g. ofl,3-di-t-butylguanylchloroformamidine hydrochloride was added slowlywith stirring to 50 cc. of 28.6% aqueous ammonia at 5-10 C. Afterstanding at room temperature for one hour, the reaction mixture wasfiltered to recover the precipitated 1,5-di-t-butylbiguanidehydrochloride. After recrystallization from ethanol the hydrochloridesalt melted at 230 C. The free base melted at 179180 C.

EXAMPLE 4 1 ,5 -di-t-butyl-4-amyl biguanide 10 g. of1,3-di-t-butylguanylchloroformamidine hydrochloride was added slowlywith stirring to a solution of 10 g. of n-amylamine in 20 cc. ofacetonitrile maintained at about 5 C. After standing at room temperaturefor two hours, the reaction mixture was poured into 100 cc. of water andfiltered to recover the precipitated 1,5-di-tbutyl-4-amylbiguanidehydrochloride. After recrystallization from ethanol the hydrochloridesalt melted at 245-246 C. The free base was formed by treating thehydrochloride salt with potassium hydroxide in aqueous solution.

EXAMPLE 5 1,I,4,4,5,5-hexamethylbiguanide 213 g. oftetramethylguanylchloroformamidine hydrochloride was added slowly withstirring to 250 g. of a 40% aqueous solution of dimethylamine. Thetemperature of the mixture rose rapidly to about 40 C. After standingfor 15 minutes, solid sodium hydroxide was added and the liquidseparated into two phases. The organic phase was separated, dried oversolid sodium hydroxide, and distilled under reduced pressure. Theproduct, a colorless liquid, distilled at 115117 C./ 1.0 mm.

EXAMPLE 6 1 ,1 ,5 ,5 -tetramethyl-4-phenylbiguanide A mixture of 21.3 g.(0.1 mol) of tetramethylguanylchloroformamidine hydrochloride, 18.6 g.(0.2 mol) of aniline and 100 cc. of acetonitrile was heated for 10minutes at reflux. The clear solution upon cooling to room temperaturedeposited 32 g. of solid material which was dissolved in 100 cc. ofwater and made basic with ammonia. The aniline which separated wasextracted with benzene and the aqueous layer was made alkaline by theaddition of sodium hydroxide. The precipitated biguanide (20 g.) wasseparated by filtration and recrystallized from cyclohexane. The whitecrystalline product melted at 8990 C.

The biguanides prepared by the method of the present invention areuseful as tarnish inhibitors in detergent compositions utilized in thewashing of household utensils such as tableware or silverware consistingof German silver and like alloys. The quantity of the tarnish inhibitorto be used is generally less than 1% by weight of the detergentcomposition, and preferably from .05 to .5 The biguanides of Examples 2,4, 5 and 6 above were tested as tarnish inhibitors by the followingmethod: alloy bars (65% copper, 18% nickel, 17% zinc) A; x V2 x 2 /2 insize were cleaned with approximately 0.7 N nitric acid, rinsed withwater and then acetone. A commercial detergent composition consisting ofapproximately 50% sodium tripolyphosphate, 25-30% alkyl-aryl sulfonate,1219% sodium sulfate and 34% sodium silicate was employed. The alloy barwas immersed in 25 cc. of detergent solution (2.5 g. of

detergent per 1500 cc. of water) containing 0.4% of the biguanidecompound (based on the weight of the detergent). The temperature of thedetergent solution was maintained at 43 C. and the period of immersionwas 7 minutes. The bar was removed from the solution, rinsed with waterand acetone, and stored under toluene for observation of tarnish film. Ablank test with the detergent solution gave a heavy tarnish film on thealloy bar, whereas tarnishing was substantially diminished with thedetergent solutions containing the biguanide compounds.

While the invention has been described with particular reference tospecific embodiments, it is to be understood that it is not to belimited thereto but is to be construed broadly and restricted solely bythe scope of the appended claims.

We claim:

1. A method of preparing a biguanide of the formula Ni ?-N=CN R: R2wherein R1 represents an alkyl radical having from 1 to 18 carbon atoms,R2 represents a member of the group consisting of hydrogen and R1, andR3 and R4 are selected from the group consisting of hydrogen, an arylradical and an alkyl radical having from 1 to 18 carbon atoms, whichcomprises reacting in an inert solvent an alkylguanylchloroformamidinehydrochloride of the formula in which R1 and R2 have the above meanings,with a member of the group consisting of ammonia, a primary amine of theformula RaNHz and a secondary amine of the formula R3R4NH wherein R3 andR4 represent members of the group consisting of an aryl radical and analkyl radical having from 1 to 18 carbon atoms, and recovering thethus-formed biguanide from the reaction mixture.

2. The method of claim 1 in which the reaction is carried out at atemperature within the range of from about 10 C. to about C.'

3. The method which comprises reacting tetraethylguanylchloroformamidinehydrochloride with ammonia in an inert solvent at a temperature withinthe range of from 10 C. to 90 C., and recoveringl,1,5,5-tetraethylbiguanide from the reaction mixture.

4. The method which comprises reactingtetramethylguanylchloroformamidine hydrochloride with dimethylamine inan inert solvent at a temperature within the range of from 10 C. to 90C., and recovering 1,1,4,4,5,5-hexamethylbiguanide from the reactionmixture.

5. The method which comprises reactingtetramethylguanylchloroformamidine hydrochloride with aniline in aninert solvent at a temperature within the range of from 10 C. to 90 C.,and recovering 1,1,5,5-tetramethyl-4- phenylbiguanide from the reactionmixture.

No references cited.

1. A METHOD OF PREPARING A BIGUANIDE OF THE FORMULA
 5. THE METHOD WHICHCOMPRISES REACTING TETRAMETHYLGUANYLCHLOROFORMAMIDINE HYDROCHLORIDE WITHANILINE IN AN INERT SOLVENT AT A TEMPERATURE WITHIN THE RANGE OF FROM10* C. TO 90* C., AND RECOVERING 1,1,5,5-TETRAMETHYL-4PHENYLBIGUANIDEFROM THE REACTION MIXTURE.